Dissolution of blood clots (fibrinolysis) requires plasmin, a protease derived from the activation of plasminogen by tissue plasminogen activator (tPA). Both plasminogen and tPA are known to bind to the surface of platelets, where their interaction becomes greatly accelerated. Therefore, platelets are important promoters of fibrinolysis. Our laboratory has been examining plasminogen binding to platelets in some detail. We use classical equilibrium binding experiments with the goal of establishing the number of binding sites and the binding affinity. We are also chemically crosslinking biotinylated plasminogen to platelets and then testing for plasminogen-receptor complexes by Western blotting, with the goal of identifying the platelet membrane protein(s) that binds plasminogen to activated and resting cells. The literature indicates that platelet activation enhances plasminogen and that the increased binding is not directly to the platelets but to platelet-bound fibrin. However, our data suggest that there is direct plasminogen binding to the platelet membrane protein IIIa and possibly to IIb. When platelets are activated with thrombin, the number of their plasminogen binding sites appears to decrease from approximately 120,000 per cell to 60,000 per cell, but the binding affinity increases several fold.